Learning disabilities (LDs) affect up to 15 percent of children and lead to poor psychosocial outcomes and school failure1. To date, research on the etiology of learning and achievement problems has focused largely on endogenous, internal factors such as genetics, intelligence, and specific cognitive abilities like phonological processing and language development2,3 with little attention paid to the contribution of exogenous, environmental factors, such as neurotoxic exposures. This K23 application presents a research and training program that will support the applicant on a path towards becoming an NIH-funded independent investigator focused on using functional magnetic resonance imaging (fMRI) to study of the effects of neurotoxic environmental exposures on brain development and the manifestation of learning and achievement problems. The activities in this application build on the candidate's prior training and are set in a resource-rich environment that will foster her development of expertise in (1) advanced analytic methods of fMRI research; (2) environmental epidemiology; and (3) theoretical models of the neural bases of learning disabilities. Through combining fMRI and environmental epidemiology, the current research proposal seeks to (1) evaluate associations between ETS exposure and neurobehavioral outcomes; and (2) define a novel phenotype of learning and achievement problems that derives from prenatal exposure to environmental tobacco smoke (ETS). The overarching hypothesis is that functional abnormalities in frontostriatal circuits in children with prenatal exposure to ETS contribute to impairments in cognitive control and academic skill deficits. The study will use fMRI to assess the functioning of frontostriatal control circuits in 40 seven-year-old children with different levels of prenatal ETS exposure, selected from a prospective cohort study. This design will allow the candidate to test a direct link between prenatal exposure to ETS, cognitive control, and academic skills, thus informing the neurobiological basis of a novel phenotype of learning and achievement problems. This training and research program will facilitate the candidate's transition to an independent research career, will help identify public health interventions to improve children's safety in the environment, and provide a viable target for early intervention and prevention of learning and achievement problems. RELEVANCE: The novel application of fMRI to the study of environmental causes of learning and achievement problems will shed light on unstudied causes of these problems, thus filling an important gap in the research literature. These data will test the concept that exogenous, preventable environmental factors contribute to the development of learning and achievement problems, thereby expanding LD research beyond its current focus on endogenous factors. Long term, results may be used to inform: 1) the development of novel therapeutics to treat this ETS-associated learning problem phenotype; and 2) public policy messaging, which currently does not provide information about ETS exposure and risk for learning problems18.